Lipid-lowering therapy of everolimus-related severe hypertriglyceridaemia in a pancreatic neuroendocrine tumour (pNET).

WHAT IS KNOWN AND OBJECTIVE: Hypertriglyceridaemia (HTG) is a potentially serious side effect of everolimus therapy. We here report a case of severe HTG in an everolimus-treated patient and provide recommendations for its management. CASE SUMMARY: The patient was a 70-year-old woman, being treated with everolimus for a pancreatic neuroendocrine tumour (pNET). She developed severe HTG to a maximum of 969 mg/dL after 22 months of therapy. Treatment with fenofibrate rapidly normalized triglyceride (TG) levels. WHAT IS NEW AND CONCLUSION: Severe HTG may occur in everolimus-treated patients. Prescription of the appropriate therapy can allow patients to continue this medication.

Mild cognitive impairment in medical inpatients: the Mini-Mental State Examination is a promising screening tool.

AIM: To assess the prevalence of mild cognitive impairment (MCI) in medical inpatients aged 55-85 years without known cognitive deficits, and how often ward physicians mentioned MCI in their discharge notes. Moreover, we aimed to identify variables associated with MCI and to assess the sensitivity and specificity of the Mini-Mental State Examination (MMSE) for MCI. METHODS: Two neuropsychologists administered a 60-min battery of validated tests to evaluate different cognitive domains. The diagnosis of MCI was based on a prespecified algorithm. The sensitivity and specificity of the MMSE for MCI were calculated. RESULTS: Fifteen patients showed a normal cognitive profile (21.4%), while 55 patients (78.6%) showed MCI. Ward physicians, blinded to the results of the neuropsychological evaluation, did not mention MCI in their discharge notes of any of the evaluated patients. The only variable independently associated with MCI was the MMSE. A MMSE score of < or =28 showed a sensitivity of 85.5% and a specificity of 66.7% for MCI. CONCLUSION: MCI is frequent albeit overlooked in elderly medical inpatients without previously known cognitive deficits. In view of therapies preventing the progression of MCI to dementia, MCI screening will be crucial. The MMSE represents a promising screening tool for MCI in medical inpatients.

Campylobacter fetus subspecies fetus bacteremia.

Eight patients with Campylobacter fetus bacteremia, six of them with serious underlying diseases, were seen in a two-year period. Besides fever, which was observed in all cases, the most frequent clinical manifestation was lower extremity phlebitis and cellulitis (four patients). In one of these patients, it had the peculiar aspect of bilateral pretibial cellulitis. One patient had vertebral osteomyelitis, a complication, to our knowledge, not yet described. Two patients, both with advanced underlying diseases, died. The five patients who completed a two- to three-week course of erythromycin gluceptate, all had initial clinical improvement. However, one patient suffered a relapse at the end of treatment, and progression of vertebral osteomyelitis while on erythromycin therapy was observed in another patient. These clinical and bacteriologic failures occurred despite the in vitro sensitivity to erythromycin of the two strains. This suggests that erythromycin might not be adequate therapy for C fetus septicemia.

Oral vs intravenous ciprofloxacin in the initial empirical management of severe pyelonephritis or complicated urinary tract infections: a prospective randomized clinical trial.

BACKGROUND: There are few data on the efficacy of oral antibiotics in the initial empirical management of severe forms of urinary tract infection (UTI). METHODS: In a multicenter, prospective, randomized trial we compared oral (500 mg twice daily) vs intravenous ciprofloxacin (200 mg twice daily) in the initial empirical management of hospitalized patients with serious forms of UTI. Exclusion criteria were severe sepsis, inability to take oral medication, or the presence of obstruction or renal foci of suppuration. The study population included 66 women with pyelonephritis, 43 patients with community-acquired UTIs, and 32 patients with hospital-acquired UTIs. The frequency of bacteremia was 28 (42%) of 66 in the patients with pyelonephritis and 25 (33%) of 75 in those with complicated UTIs. Seventy-two patients were randomized to treatment with oral and 69 to intravenous ciprofloxacin. RESULTS: There were no infection-related deaths and no patients required an early change of antibiotics because of worsening clinical status during the initial empirical phase of treatment. The mean duration of fever was 1.7 days in patients treated by the oral vs 1.9 days in patients treated by the intravenous route (P = .15). The rates of microbiological failure (3% in the oral vs 2% in the intravenous treatment group) and of unsatisfactory clinical response (4% oral vs 3% intravenous) were low. A treatment change was eventually required in 14% of the patients assigned to the oral and 7% of the patients assigned to the intravenous regimen, mainly because of the isolation of enterococci or ciprofloxacin-resistant organisms in pretherapy urine specimens. CONCLUSIONS: In the hospital setting, oral ciprofloxacin is as effective as the intravenous regimen in the initial empirical management of serious UTIs, including bacteremic forms, in patients without severe sepsis, obstruction, or renal foci of suppuration. The efficacy of the oral regimen indicates a potential use for ciprofloxacin in outpatient treatment of a subset of patients currently hospitalized on account of disease severity.

Hemostatic activation under anticoagulant treatment: a comparison of unfractionated heparin vs. nadroparin in the treatment of proximal deep vein thrombosis.

BACKGROUND: Multiple clinical trials have been performed to compare standard heparin with low molecular weight heparin in the therapy of deep vein thrombosis, but little is known about the time course of the markers of hemostatic system during the treatment with these two heparin regimens. METHODS: Twenty patients with proximal deep vein thrombosis confirmed by duplex ultrasound and phlebography were randomly assigned to either unfractionated heparin (UH) given as an intravenous bolus of 80 U/kg followed by a constant infusion of 18 U/kg/h, or nadroparin 185 AXa IU/kg once daily subcutaneously. Oral anticoagulants were started at day 4. Markers of hemostatic activation (F1+2, FPA, TAT, D-dimer) were measured daily for 4 days. Primary endpoints were the time course of these markers; secondary endpoints consisted in the evaluation of thromboembolic and hemorrhagic complications by clinical outcome and Marder score. RESULTS: Treatment with UH resulted in a rapid achievement of therapeutic heparin levels. UH reduced markers of fibrin formation and fibrinolysis more rapidly than nadroparin (p < 0.05). Within the nadroparin group activation of prothrombotic markers four hours after the subcutaneous injection (peak level) was significantly lower when compared with the time prior to injection (trough level). Secondary endpoints showed no significant difference between the two groups. CONCLUSION: Continuous intravenous perfusion of UH administered on a basis of a weight-adjusted nomogram controlled markers of the hemostatic system more rapidly than once-daily subcutaneously administered weight-adjusted nadroparin.

Relationship between fibrinopeptide A and fibrinogen/fibrin fragment E in thromboembolism, DIC and various non-thromboembolic diseases.

Increased fibrinopeptide A (FPA) levels have been reported in various non-thrombotic disorders, including cancer, acute myocardial infarction, liver cirrhosis and collagen vascular diseases. To investigate the significance of these findings, the present study combined the radioimmunoassay of FPA with that of fibrinogen/fibrin degradation fragment E (FgE) in the aforementioned disorders and compared the results with those observed in healthy subjects as well as in patients with thromboembolism and overt disseminated intravascular coagulation (DIC). Mean FPA and FgE in malignancy were 6.3 and 305 ng/ml, in myocardial infarction 5.6 and 98 ng/ml, in liver cirrhosis 2.7 and 132 ng/ml and in collagen vascular diseases 5.6 and 142 ng/ml. All these values were significantly higher than in healthy controls (mean FPA 1.6 ng/ml, mean FgE 49 ng/ml) but significantly lower than in thromboembolism (mean FPA 10.7 ng/ml, mean FgE 639 ng/ml). and DIC (mean FPA 22.0 ng/ml, mean FgE 1041 ng/ml). The overall correlation between FPA and FgE was highly significant. However, different disorders showed peculiar patterns in FPA, FgE and fibrinogen levels. In malignancy, a definite increase of FPA, FgE and plasma fibrinogen levels was observed. This finding probably indicates a compensated state of (intra- or extravascular) fibrin formation and lysis. Acute myocardial infarction was characterized by a high FPA to FgE ratio, which is interpreted to reflect acute thrombin generation and fibrin formation. FPA in cirrhosis was only marginally elevated with most single values within the normal range, indicating that intravascular coagulation was infrequent and unimportant in quantitative terms.

Spontaneous biliothorax (thoracobilia) following cholecystopleural fistula presenting as an acute respiratory insufficiency. Successful removal of gallstones from the pleural space.

A patient presented to the emergency department with tachypnea, fever, a right pleural effusion, and lung consolidation. The computed tomographic guided thoracentesis yielded a greenish fluid with bilirubin. The ultrasound examination demonstrated a distended gallbladder with stones, positioned on the ventral face of the liver and a free communication between the fundus and the pleural cavity. The cholecystopleural fistula was confirmed at operation.

Gram-negative bacillary meningitis in neurosurgical patients.

The authors report 34 cases of Gram-negative bacillary meningitis related to traumatic cranial lesions or neurosurgery observed between 1973 and 1980 at two neurosurgical units (Institut J. Bordet, Brussels, and Inselspital, Bern). As a typical nosocomial infection, meningitis developed after prolonged hospitalization in most patients, and was mainly due to highly resistant organisms, such as P. aeruginosa and Klebsiella sp. At least 65% of the patients were colonized with the pathogen responsible for the meningitis before the onset of the infection. Ventriculitis, including four cases of ventricular empyema, complicated meningitis in all the 17 patients in whom a ventricular tap was performed. The results of treatment were unsatisfactory. Fifty percent of the patients were cured of their infection, but only 30% survived; 15% of the patients died within 48 hours following diagnosis. The optimum treatment of postsurgical Gram-negative meningitis remains in doubt. The choice of initial antibiotics should take into account the sensitivity patterns of colonizing microorganisms. Chloramphenicol is ineffective against most pathogens commonly involved in this infection. Intrathecal aminoglycosides may fail in the presence of ventriculitis. Intraventricular aminoglycosides are probably justified in critically ill patients. The role of the newer cephalosporins and of co-trimoxazole remains to be defined.

Post neurosurgery Gram-negative bacillary meningitis.

The findings of a retrospective analysis of 20 patients who developed Gram-negative bacillary meningitis (GNBM) following neurosurgery are reported. The predisposing causes included surgery for skull fracture or cerebral contusion (9 patients), neoplasm (6) and vascular disease (2). Nine of the patients (45 per cent) had a cerebrospinal fluid (CSF) leak from a fistula. The organisms isolated, which included Pseudomonas aeruginosa (6), Klebsiella spp. (5) and Escherichia coli (4), had, in 75 per cent of cases, been isolated from other sites prior to the onset of GNBM. Initial diagnosis was achieved by Gram-stain of CSF in 15 of 19 cases (78 per cent). Culture of lumbar CSF was positive in 19 of the patients (95 per cent) and concommittant ventriculitis was confirmed by positive culture of ventricular CSF in 10 of 11 cases (91 per cent) from whom it was obtained. The overall mortality was 80 per cent, 11 patients dying of causes directly related to GNBM. Eradication of the infecting organism from CSF was achieved in 79 per cent of patients receiving intraventricular aminoglycoside therapy, but in only 40 per cent of those receiving intralumbar therapy. Deaths in the latter group were associated with ventriculitis whereas those in patients receiving intraventricular therapy resulted from intracranial abscess formation. These findings, plus the observation of chloramphenicol resistance in 80 per cent of the isolates, suggest that systemic and intraventricular aminoglycoside administration is indicated in patients with post-neurosurgical GNBM.

Homocysteine, vitamins and gene mutations in peripheral arterial disease.

A case-control study was undertaken involving 51 consecutive patients with peripheral artery obstructive disease (PAOD) scheduled for angioplasty. Blood samples of these patients were analysed for plasma homocysteine (tHcy) and levels of vitamin B12 and folate, and the MTHFR gene was assessed for mutation. Patients were compared with age- and sex-matched controls who did not present with cardiovascular risk factors. Mean tHcy did not differ between cases and controls (13.3 +/- 5.7 and 12.6 +/- 4.9 micromol/l, P = 0.49). More patients were above the 95th percentile as determined from the data in the control group with an odds ratio (OR) that almost reached statistical significance [OR, 2.8; 95% confidence interval (CI), 0.9-8.7], but on separate analyses only female patients showed higher tHcy than female controls (15.6 versus 12.0 micromol/l, P = 0.05), with an odds ratio for tHcy above the 95th percentile of 10.5 (95% CI, 1.1-96.6). The TT genotype of the MTHFR gene was found in 24% of the patients and in 12% of the controls (OR, 2.3; 95% CI, 0.8-6.7). Our findings point to a modest association between tHcy and PAOD, with a difference between cases and controls restricted to the highest percentile in female patients. A weak but not significant association was also found for the TT genotype of the MTHFR gene.

Angiotropic (intravascular) large cell lymphoma: case report and short discussion of the literature.

We report a case of angiotropic (intravascular) large B-cell lymphoma in an 84-year-old woman who underwent diagnostic procedures for progressive, painful induration of the legs. Physical examination and imaging studies revealed only widespread telangiectasias and significant panniculities-like lymphedema of the legs, with no masses or lymphadenopathies. The patient achieved a complete clinical remission after the first three cycles of polychemotherapy. Although angiotropic lymphoma is a rare entity with polymorphic clinical presentations, its early diagnosis appears very important since it may be curable with appropriate chemotherapy regimens.

[Skin necroses, thrombocytopenia and deep venous thrombosis in subcutaneous thromboembolism prophylaxis with heparin: heparin-induced thrombocytopenia (HIT) type II]. / Hautnekrosen, Thrombozytopenie und tiefe Beinvenenthrombose unter subkutaner Thromboembolieprophylaxe mit Heparin: Heparininduzierte Thrombozytopenie (HIT) Typ II.

We present a 52-year-old woman who developed a heparin-induced thrombocytopenia type II (HIT II) with deep vein thrombosis, thrombocytopenia and skin necrosis 7 days after initiating subcutaneous prophylaxis with 2 x 5000 U of unfractionated heparin. The platelet count fell from an initial value of 233 x 10(9)/L to 57 x 10(9)/L and normalized within 3 days after stopping heparin. Oral phenprocoumon was started, and her further course was uneventful. The pathogenesis and diagnosis of HIT II is illustrated, and the possible therapeutic options are discussed. To prevent this potentially lethal complication, it is important to begin oral anticoagulation on the first or second day of heparinization, and to stop heparin if the INR-value has been within a therapeutic range for 2 consecutive days. Platelet counts must be checked after 5 to 7 days of heparin therapy. In the case of suspected HIT II, a diagnostic test has to be performed, the heparin must be stopped, and an anticoagulation with either danaparoid or lepirudin is recommended.

[Useful and superfluous measures in the treatment of respiratory infections]. / Sinnvolles und Uberflüssiges in der Behandlung respiratorischer Infekte.

A safe and inexpensive approach to respiratory infections requires: 1. an accurate diagnosis, 2. a critical attitude towards drugs whose clinical efficacy is unproven, 3. to avoid antibiotics where they are not strictly indicated, 4. to use penicillin instead of more expensive (and often less active) antibiotics in the treatment of infections due to streptococci or pneumococci.

Individual dosage of digoxin in patients with heart failure.

BACKGROUND: After the publication of DIG trial, the therapeutic target of serum digoxin concentration (SDC) for the treatment of heart failure (HF) has been lowered (0.40-1.00 ng/ml). However, the majority of equations to calculate digoxin dosages were developed for higher SDCs. Recently, a new equation was validated in Asian population for low SDCs by Konishi et al., but results in Caucasians are unknown. AIM: This study was aimed to test the Konishi equation in Caucasians specifically targeting low SDCs. Furthermore, the Konishi equation was compared with other frequently used equations. DESIGN: This was a prospective, multicenter study. METHODS: Clinically indicated digoxin was given in 40 HF patients. The dosage was calculated with the Konishi equation. The SDC was measured at 1 and 6 months after starting digoxin. Adherence to digoxin was monitored with a specific questionnaire. RESULTS: After exclusion of patients admitting poor adherence, we found a reasonable correlation between predicted and measured SDC (r=0.48; P<0.01) by the Konishi equation. Excluding patients with poor adherence and relevant worsening of renal function, the measured SDC (n=54 measurements) was within the pre-defined therapeutic range in 95% of the cases. The mean, maximal and minimal measured SDC were 0.69±0.19, 1.00 and 0.32 ng/ml, respectively. The correlation was weaker for the Jelliffe, the Koup and Jusko, and the Bauman equations. CONCLUSION: This study supports the clinical validity of the Konishi equation for calculating individual digoxin dosage in Caucasians, targeting SDCs according to current HF guidelines.

[Fever with chills]. / Der Schüttelfrost.

Abrupt onset of fever with chills represents a body response to various stimuli called exogenous pyrogens. These substances interact with monocytes and macrophages, thus releasing various cytokines including interleukin-1 and tumor necrosis factor (endogenous pyrogens). Endogenous pyrogens act centrally on the thermosensitive neurons in the hypothalamus to increase the core body temperature by increasing heat production and decreasing heat loss. In addition, endogenous pyrogens trigger a non-specific inflammatory response and amplify the specific immune response through activating the T- and B-cell system. Pyogenic infections are the most frequent and most important cause of abrupt onset of fever with chill, but a similar pattern of fever may occur in many other situations. In many instances, a thorough history and a complete physical examination will produce a presumptive diagnosis. Further management decisions depend on the clinical conditions and on the localization of the infection. Patients with compromised vital functions, with involvement of the central nervous system, with chills associated with prolonged fever without localizing symptoms or physical findings, or with symptoms of intraabdominal sepsis, must be promptly hospitalized. The most important aspects of treatment should be directed at the cause of fever, and antipyretic drugs should be used after evaluation of relative risks in the individual case.